Our long term objective is to develop tetravalent IgG/IgG monoclonal antibody dimers for treating leukemia and lymphoma patients over-expressing the CD23 membrane antigens. Preliminary data using both CD20 and CD23 B-cell membrane antigens has clearly demonstrated that hyper-cross linking induces both apoptosis and growth inhibition. In contrast, direct binding of monomeric monoclonal antibody (mAb) to membrane antigen was inefficient. The process developed allows for the preparation of biologically active mAb dimers that retain full effector functions, using a genetically engineered antibody having the cysteine reactive thiol introduced at a specific site on the heavy chain. By careful selection of the site for thiol introduction, dimers should be produced having excellent yields and a superior biological profile than monomeric mAb. PROPOSED COMMERCIAL APPLICATION: The goal of this project is to develop a tetravalent anti-CD23 antibody dimer that will allow for more potent and effective treatment for chronic lymphocytic leukemia.